Self-reported non-adherence to P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: Application of the medication non-adherence academic research consortium classification

Abstract

Aims: The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).

Methods and results: Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (<30 days) in 21%, late (30-180 days) in 45%, and very late (>180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE.

Conclusions: In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts.

Clinicaltrials.gov identifier: NCT02241291.

Conflict of interest statement

The authors have read the journal’s policy and have the following competing interests to declare: YU reports personal fees from Infraredex, outside the submitted work. GCMS reports personal fees from Abbott Vascular, outside the submitted work. JH reports personal fees from Bayer, outside the submitted work. SS reports grants from Edwards Lifesciences, grants from Medtronic, grants from Abbott Vascular, grants and personal fees from Boston Scientific, personal fees from BTG, outside the submitted work. TP reports grants and personal fees from Biotronik, grants and personal fees from Symetis/Boston Scientific, grants from Edwards Lifesciences, and personal fees from HighLife SAS outside the submitted work. MV reports grants and personal fees from Terumo, grants from Medicure, grants and personal fees from Abbott, grants and personal fees from Astrazeneca, personal fees from Chisei, personal fees from Bayer, personal fees from Daiichi Sankyo, personal fees from Amgen, personal fees from Alvimedica, personal fees from Biosensors, outside the submitted work. SW reports research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Johnson&Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, Sinomed. SW serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. SW is an unpaid member of the Pfizer Research Award selection committee in Switzerland. LR reports grants and personal fees from Abbott Vascular, personal fees from Amgen, personal fees from Astra Zeneca, grants and personal fees from Biotronik, grants and personal fees from Sanofi, grants from Heartflow, personal fees from Canon, personal fees from Occlutech, outside the submitted work. The other authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Figures

Fig 1. Patient flow.

DAPT = dual antiplatelet therapy, PCI = percutaneous coronary intervention.

Fig 2. Overview of non-adherence according to NARC classification.

NARC = non-adherence academic research consortium.

Fig 3. Kaplan-Meier cumulative event curve for POCE at 1 year.

POCE = patient-oriented composite endpoints.

Fig 4. Multivariable Cox analysis for POCE at 1 year according to non-adherence levels.

Of the study patients, 90.4% (3525 of 3896 patients) were included in the multivariable models. The following covariates were entered in the models: age, female sex, diabetes mellitus, eGFR, peripheral artery disease, myocardial infarction at presentation, cardiogenic shock, chronic obstructive lung disease, history of cancer, history of PCI, and use of new generation DES. CI = confidence interval, DAPT = dual antiplatelet therapy, DES = drug eluting stent, eGFR = estimated glomerular filtration rate, HR = hazard ratio, PCI = percutaneous coronary intervention.